Lectures 2014 – 2015
Physiology and the concept of homeostasis
Physiology is the study of the functions of the animal body. In other words, the
mechanisms by which the various organs and tissues carry out their specific activities
are considered .
The goal of physiology is to explain the physical and chemical factors that are
responsible for the origin, development, and progression of life.
The body to function optimally, conditions within the body, referred to as the internal
environment, must be very carefully regulated.
Therefore, many important variables, such as body temperature, blood pressure, blood
glucose, oxygen and carbon dioxide content of the blood, as well as electrolyte
balance, are actively maintained within narrow physiological limits.
Cells as the Living Units of the Body
The basic living unit of the body is the cell. Each organ is an aggregate of many
different cells held together by intercellular supporting structures. Each type of cell is
specially adapted to perform one or a few particular functions. For instance, the red
blood cells, transport oxygen from the lungs to the tissues.
Body fluids
About 60 percent of the adult animal body is fluid, mainly a water solution of ions
and other substances. Although most of this fluid is inside the cells and is called
intracellular fluid, about one third is in the spaces outside the cells and is called
extracellular fluid. This extracellular fluid is in constant motion throughout the body.
It is transported rapidly in the circulating blood and then mixed between the blood and
the tissue fluids by diffusion through the capillary walls. In the extracellular fluid are
the ions and nutrients needed by the cells to maintain cell life. Thus, all cells live
in essentially the same environment—the extracellular fluid. For this reason, the
extracellular fluid is also called the internal environment of the body, or the milieu
intérieur, a term introduced more than 100 years ago by the great 19th-century
French physiologist Claude Bernard.
Homeostasis
The term homeostasis is used by physiologists to mean maintenance of nearly
constant conditions in the internal environment. It is important because the cells and
tissues of the body will survive and function efficiently only when these internal
conditions are properly maintained.
The body is constantly faced with a changing external environment as well as with
events and activities occurring within it that may alter the balance of important
variables. For example, most metabolic reactions within cells consume oxygen and
glucose.
These substances must then be replaced. In addition, these reactions produce
metabolic wastes including carbon dioxide and urea, which must then be eliminated.
Therefore, it is more accurate to say that the internal environment is in a dynamic
steady state — one that is constantly changing, but in which optimal conditions are
physiologically maintained.
All of the organ systems in the body, except the reproductive system, contribute to the
maintenance of homeostasis . For example, the gastrointestinal tract digests foods to
provide nutrients to the body. The respiratory system obtains oxygen and eliminates
carbon dioxide. The circulatory system transports all of these materials and others
from one part of the body to another. The renal system eliminates wastes and plays a
role in regulating blood volume and blood pressure.
Two regulatory systems in the body influence the activity of all the other organ
systems so that homeostasis is ultimately maintained:
1-Nervous system : The sensory division of the peripheral nervous system is sensitive
to changes in the internal and external environment. The information gathered by this
component is transmitted to the CNS where it is processed, integrated, and
interpreted. The CNS then determines the appropriate response to this input. This
response is carried out by the transmission of nerve impulses in the motor division of
the peripheral nervous system the effector tissues.
2-Endocrine system : The other regulatory system in the body contributing to the
maintenance of homeostasis is the endocrine system, which carries out its effects by
secreting hormones. These hormones are transported in the blood to the specific
tissues upon which they exert their effects. In general, the nervous system primarily
regulates muscular activity and glandular secretion and the endocrine system
primarily regulates metabolic activity in the body’s cells. However, these two systems
may work together in the regulation of many organs, as well as influence each other’s
activity.
Negative feedback
Most of the body’s compensatory homeostatic mechanisms function by way of
negative feedback. This is a response that causes the level of a variable to change in a
direction opposite to that of the initial change. For example, when blood pressure
increases, the arterial baroreceptors are stimulated and an increased number of nerve
impulses are transmitted to the CNS through afferent pathways. The region of the
brain regulating the cardiovascular system responds to this sensory input by altering
efferent nerve activity to the heart. The result is a decrease in heart rate and therefore
a decrease in blood pressure back to its baseline value. In general, when a
physiological variable becomes too high or too low, a control system elicits a negative
feedback response consisting of one or a series of changes that returns the variable to
within its normal physiological range. These compensatory mechanisms operating via
negative feedback allow the body to maintain homeostasis effectively.
Positive Feedback
Most control systems of the body operate by negative feedback rather than positive
feedback . Positive feedback is better known as a “vicious cycle,” but in some
instances, the body uses positive feedback to its advantage. Blood clotting is an
example of a valuable use of positive feedback. When a blood vessel is ruptured and
a clot begins to form, multiple enzymes called clotting factors are activated within the
clot itself. Some of these enzymes act on other unactivated enzymes of the
immediately adjacent blood, thus causing more blood clotting. This process continues
until the hole in the vessel is plugged and bleeding no longer occurs.
Childbirth is another instance in which positive feedback plays a valuable role. When
uterine contractions become strong enough for the baby’s head to begin pushing
through the cervix, stretch of the cervix sends signals through the uterine muscle back
to the body of the uterus, causing even more powerful contractions. Thus, the uterine
contractions stretch the cervix and the cervical stretch causes stronger contractions.
When this process becomes powerful enough, the baby is born. If it is not powerful
enough, the contractions usually die out and a few days pass before they begin again.
The Cell
Each one of the cells in an animal is a living structure that can survive for months or
many years. Its two major parts are the nucleus and the cytoplasm. The nucleus is
separated from the cytoplasm by a nuclear membrane, and the cytoplasm is separated
from the surrounding fluids by a cell membrane, also called the plasma membrane.
The different substances that make up the cell are collectively called protoplasm.
Protoplasm is composed mainly of five basic substances: water, electrolytes, proteins,
lipids, and carbohydrates.
Plasma membrane
Each cell is surrounded by a plasma membrane that separates the cytoplasmic
contents of the cell, or the intracellular fluid, from the fluid outside the cell,
the extracellular fluid. An important homeostatic function of this plasma membrane
is to serve as a permeability barrier that insulates or protects the cytoplasm
from immediate changes in the surrounding environment. Furthermore, it
allows the cell to maintain a cytoplasmic composition very different from that
of the extracellular fluid; the functions of neurons and muscle cells depend on
this difference. The plasma membrane also contains many enzymes and other
components such as antigens and receptors that allow cells to interact with
other cells, neurotransmitters, blood-borne substances such as hormones, and
various other chemical substances, such as drugs.
Structure and function of plasma membrane
The major components of the plasma membrane include:
1-Phospholipids
2- Cholesterol
3-Proteins
4- Carbohydrates
The basic structure of the plasma membrane is formed by phospholipids , which are
one of the more abundant of the membrane components.
Phospholipids are amphipathic molecules that have polar (water-soluble) and
nonpolar (water-insoluble) regions. They are composed of a phosphorylated
glycerol backbone, which forms a hydrophilic polar head group and a nonpolar region
containing two hydrophobic fatty acid chains. In an aqueous environment such as the
body, these molecules are arranged in a formation referred to as the lipid bilayer
consisting of two layers of phospholipids.
The polar region of the molecule is oriented toward the outer surface of the membrane
where it can interact with water; the nonpolar, hydrophobic fatty acids are in the
center of the membrane away from the water. The functional significance of this lipid
bilayer is that it creates a semipermeable barrier . Lipophilic, or nonwater-soluble,
substances can readily cross the membrane by simply passing through its lipid core.
Important examples of these substances include gases, such as oxygen and carbon
dioxide, and fatty acid molecules, which are used to form energy within muscle cells.
Most hydrophilic, or water-soluble, substances are repelled by this hydrophobic
interior and cannot simply diffuse through the membrane. Instead, these substances
must cross the membrane using specialized transport mechanisms. Examples of lipidinsoluble substances that require such mechanisms include nutrient molecules, such as
glucose and amino acids, and all species of ions (Na+ , Ca++ , H+ , Cl– , and HCO3).
Therefore, the plasma membrane plays a very important role in determining the
composition of the intracellular fluid by selectively permitting substances to move in
and out of the cell.
Another important aspect of the lipid bilayer is that the phospholipids are not held
together by chemical bonds. This enables molecules to move about freely within the
membrane, resulting in a structure that is not rigid in nature, but instead, very fluid
and pliable. Also contributing to membrane fluidity is the presence of cholesterol.
Cholesterol prevents the fatty acid chains from packing together and crystallizing,
which would decrease membrane fluidity. Membrane fluidity is very important in
terms of function in many cell types. For example, skeletal muscle activity involves
shortening and lengthening of muscle fibers. Furthermore, as white blood cells leave
the blood vessels and enter the tissue spaces to fight infection, they must squeeze
through tiny pores in the wall of the capillary requiring significant deformation of the
cell and its membrane. Finally, in all cells, many processes that transport substances
across the plasma membrane require the embedded proteins to change their
conformation and move about within the bilayer.
In each case, in order for the cell membrane, or the entire cell, to change its
shape, the membrane must be very fluid and flexible.
Proteins
are also associated with the lipid bilayer and essentially float within it. Intrinsic
proteins are embedded within and span the membrane, and extrinsic proteins are
found on the internal or external surface of the membrane . These proteins provide a
variety of important cellular functions by forming the following structures:
• Channels
• Carrier molecules
• Enzymes
• Chemical receptors
• Antigens
Some proteins may form channels through the cell membrane that allow small, watersoluble substances such as ions to enter or leave the cell. Other proteins may serve as
carrier molecules that selectively transport larger water-soluble molecules, such as
glucose or cellular products, across the membrane. Regulators of specific chemical
reactions, enzymes are extrinsic proteins found on the internal (e.g., adenylate
cyclase) or external (e.g., acetylcholinesterase) surfaces of the membrane.
Chemical receptors are found on the outer surface of the cell membrane and
selectively bind with various endogenous molecules as well as with drugs. Through
receptor activation, many substances unable to enter the cell and cause a direct
intracellular effect may indirectly influence intracellular activity without actually
crossing the membrane.
Other proteins found on the external surface of the plasma membrane are antigens .
These molecules serve as cell “markers” that allow the body’s immune system to
distinguish between its own cells and foreign cells or organisms such as bacteria and
viruses.
The plasma membrane contains a small amount of carbohydrate (2 to 10% of the mass
of the membrane) on the outer surface. This carbohydrate is found attached to most of
the protein molecules, forming glycoproteins, and to some of the phospholipid
molecules (<10%), forming glycolipids. Consequently, the external surface of the cell
has a carbohydrate coat, or glycocalyx.
These carbohydrate moieties have several important functions, including:
• Repelling negatively charged substances: many of the carbohydrates are negatively
charged, creating an overall negative charge on the surface of the cell that repels
negatively charged extracellular molecules.
• Cell-to-cell attachment: the glycocalyx of one cell may attach to the glycocalyx of
another cell, which causes the cells to become attached.
• Receptors: carbohydrates may also serve as specific membrane receptors for
extracellular substances such as hormones.
• Immune reactions: carbohydrates play a role in the ability of cells to distinguish
between “self” cells and foreign cells.
Membrane transport
The lipid bilayer arrangement of the plasma membrane renders it selectively
permeable. Uncharged or nonpolar molecules, such as oxygen, carbon dioxide,
and fatty acids, are lipid soluble and may permeate through the membrane
quite readily. Charged or polar molecules, such as glucose, proteins,
and ions, are water soluble and impermeable, unable to cross the membrane
unassisted. These substances require protein channels or carrier molecules
to enter or leave the cell.
Passive diffusion through the membrane
Molecules and ions are in constant motion and the velocity of their motion is
proportional to their temperature. This passive movement of molecules and ions from
one place to another is referred to as diffusion . When a molecule is unevenly
distributed across a permeable membrane with a higher concentration on one side and
a lower concentration on the opposite side, there is said to be a concentration gradient
or a concentration difference. Although all of the molecules are in motion, the
tendency is for a greater number of molecules to move from the area of high
concentration toward the area of low concentration. This uneven movement of
molecules is referred to as net diffusion.
The net diffusion of molecules continues until the concentrations of the substance on
both sides of the membrane are equal and the subsequent movement of molecules
through the membrane is in a dynamic equilibrium . In other words, the number of
molecules moving in one direction across the membrane is equal to the number of
molecules moving in the opposite direction. At this point, although the diffusion of
molecules continues, no further net diffusion takes place.
The movement of ions, in particular, depends not only on a concentration gradient but
also on an electrical gradient . Positively charged ions (cations) are attracted to a
negatively charged area and negatively charged ions (anions) are attracted to a
positively charged area. Ions of a similar charge tend to repel each other and oppose
diffusion.
Diffusion of Ions Through Protein Channels
integral membrane proteins can span the lipid bilayer. Some of these proteins form
channels that allow ions (such as Na+, K+, Cl–, and Ca2+ ) to diffuse across the
membrane. Ion channels can exist in an open or closed state , and changes in a
membrane’s permeability to ions can occur rapidly as these channels open or close.
The process of opening and closing ion channels is known as channel gating,
like the opening and closing of a gate in a fence.
Three factors can alter the channel protein conformations, producing changes in how
long or how often a channel opens. First, the binding of specific molecules to channel
proteins produce change in the shape of the channel protein. Such channels are
termed ligand-gated channels, and the ligands that influence them are often chemical
messengers. Second, changes in the membrane potential can cause movement of the
charged regions on a channel protein, altering its shape—these are voltagegated
channels. Third, physically deforming (stretching) the membrane may affect the
conformation of some channel proteins— these are mechanically-gated channels. A
particular type of ion may pass through several different types of channels. For
example, a membrane may contain ligand-gated K+ channels, voltage-gated K+
channels, and mechanically-gated K+ channels. Moreover, the same membrane
may have several types of voltage-gated K+ channels, each responding to a different
range of membrane voltage, or several types of ligand-gated K+ channels, each
responding to a different chemical messenger.
Facilitated Diffusion
Facilitated diffusion uses a transporter to move solute “downhill” from a higher to a
lower concentration across a membrane. Neither diffusion nor facilitated diffusion is
coupled to energy (ATP) derived from metabolism. Thus, they are incapable of
moving solute from a lower to a higher concentration across a membrane.
Among the most important facilitated-diffusion systems in the body are those that
move glucose across plasma membranes. Without such glucose transporters, cells
would be virtually impermeable to glucose, a relatively large, polar molecule.
Osmosis
Osmosis is the net movement of water through a semipermeable membrane down its
own concentration gradient from an area of high water concentration to an area of low
water concentration. In other words, water moves toward an area of higher solute
concentration. The osmotic pressure of a solution is the pressure or force by which
water is drawn into the solution through a semipermeable membrane.
The osmolarity of the extracellular fluid is normally in the range of 285–300 mOsm.
If a RBC is placed in a solution of 300 mOsm, they will neither swell nor shrink
because the water concentrations in the intra- and extracellular fluid are the same, and
the solutes cannot leave or enter. Such solutions are said to be isotonic. By contrast,
hypotonic solutions have a solute concentration lower than that found in cells, and
therefore water moves by osmosis into the cells, causing them to swell. Similarly,
solutions containing greater than 300 mOsm of solutes (hypertonic solutions) cause
cells to shrink as water diffuses out of the cell into the fluid with the lower water
concentration.
Active transport
With active transport , energy is expended to move a substance against its
concentration gradient from an area of low concentration to an area of high
concentration. This process is used to accumulate a substance on one side
of the plasma membrane or the other. The most common example of active
transport is the sodium–potassium pump that involves the activity of Na+
–K+ ATPase, an intrinsic membrane protein. For each ATP molecule hydrolyzed
by Na+ –K+ ATPase, this pump moves three Na+ ions out of the cell and two K+
ions into it.
Two means of coupling an energy flow to transporters are known: (1) the direct use of
ATP in primary active transport, and (2) the use of an electrochemical gradient
across a membrane to drive the process in secondary active transport.
One of the best studied examples of primary active transport is the movement of
sodium and potassium ions across plasma membranes by the Na+/K+-ATPase pump.
Secondary active transport is distinguished from primary active transport by its use of
an electrochemical gradient across a plasma membrane as its energy source, rather
than phosphorylation of a transport molecule by ATP. In secondary active
transport, the movement of an ion down its electrochemical gradient is coupled to the
transport of another molecule, such as a nutrient like glucose or an amino acid.
The movement of the actively transported solute can be either in the same direction as
sodium, in which case it is known as cotransport, or opposite the direction of
sodium movement, which is called countertransport . The terms symport and
antiport are also used to refer to the processes of cotransport and countertransport,
respectively.